CEST for Chemical Exchange dependent Saturation Transfer (CEST) agents contain a proton with a resonant frequency well enough removed from that of the dominant water line present in most samples that the agent resonance can be saturated by an RF field that has little direct effect on the water. If the resonant proton exchanges chemically with the bulk water, the water magnetization decreases. Under favorable conditions, repeated exchanges can decrease the water magnetization by much more than the total magnetization the agent has at any one time. This multiplier greatly enhances sensitivity.
CEST allows quantitation of a sample property and demonstrated a pH determination. Similar quantitation is very difficult with relaxation-based agents. To see this difficulty, consider an agent whose relaxivity varies in a known way with pH. A measurement of sample signal or even of sample relaxation rate does not give the pH because the relaxation rate depends on concentration as well as pH. In general, contrast agent concentration cannot be predicted in advance, or there would be no point in giving them. Concentration could be determined from relaxation rate for an ordinary relaxation agent with known relaxivity. For the hypothetical pH sensitive contrast agent however, the relaxivity is not known unless the pH is known, in which case there is no need for the agent.
This problem may be solved with a ‘dual agent,’ one having exchangeable protons with two different resonant frequencies. One type of proton had a pH dependent exchange lifetime; the other type had a pH independent lifetime. Dividing the effect of irradiating one of the resonances by the effect of irradiating the other cancelled the effect of the unknown concentration. For the dual agent method to work as demonstrated by Ward and Balaban, it is necessary that RF irradiation be strong enough to saturate the magnetization of the agent bound protons fully. This much RF may be unsafe for human studies or for large animals.